Higher-Density Culture in Human Embryonic Stem Cells Results in DNA Damage and Genome Instability

In this study, the authors elucidate a direct relationship between culture density and the emergence of DNA damage and genomic alterations in human embryonic stem cells (hESC). Compared with culture on feeder cells, hESCs cultured on laminin-521 (LN521) exhibit reduced susceptibility to DNA damage under suboptimal culture conditions, such as medium acidification during high-density culture. This phenomenon leads to an accumulation of cells in the G1 phase and a halt in the S phase, without concomitant cell death or loss of pluripotency. Remarkably, these DNA effects manifest rapidly, occurring within a single passage.